Modulation of Angiotensin II Binding and AT1 Receptor Expression in Experimental Alport Mouse Kidney

Nova Southeastern University, Davie, Florida, USA

Objective: To measure AT1 angiotensin II (AngII) receptor (AT1R) expression in an animal model of Alport Syndrome (AS) to assess the association between these receptors and this disease. Background: AS is a progressive renal glomerular disease, causing kidney failure, and hearing and visual impairment, affecting up to 3% of children and 0.2% of adults with end-stage renal disease (ESRD). It is caused by mutation of a Type IV collagen gene. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) are the only treatments that slow progression towards ESRD in AS. Methods: Kidneys from 8-week-old Col4a3-/- (KO) and wild-type mice were assayed for AT1R using 125I-sarcosine1,isoleucine8AngII saturation binding assay and receptor autoradiography to determine receptor density, distribution and binding affinity. Results: There was a 48% decrease (pDvalues did not differ between the groups. Receptor autoradiography showed no difference in AT1R density between the groups (153 versus 149 fmoles/g wet weight). However, AT1R’s were more diffusely distributed in the KO kidneys. Conclusion: The density of AT1 receptors in the AS model kidney is reduced. This suggests that renoprotection with ACEi-ARB in AS is not linked to overexpression of renal AT1R. Funding: Peggy and Harold Katz Family Endowed Professorship (AF), Cardiovascular Neuroscience Fund.